Abstract：
OBJECTIVE: The current research on single-nucleotide polymorphism (SNP) mutation sites at different positions of the FAM83H gene and their phenotypic changes leading to amelogenesis imperfecta (AI) is inconsistent. We identified a previously reported heterozygous nonsense mutation c.1192C>T (p.Q398*) in the FAM83H gene and conducted a comprehensive analysis of the dental ultrastructure and chemical composition changes induced by this mutation. Additionally, we predicted the protein feature affected by this mutation site. The aim was to further deepen our understanding of the diversity of AI caused by different mutation sites in the FAM83H gene.
METHODS: Whole-exome sequencing (WES) and Sanger sequencing were used to confirm the mutation sites. Physical features of the patient\'s teeth were investigated using various methods including cone beam computer tomography (CBCT), scanning electron microscopy (SEM), contact profilometry (roughness measurement), and a nanomechanical tester (nanoindentation measurement). The protein features of wild-type and mutant FAM83H were predicted using bioinformatics methods.
RESULTS: One previously discovered FAM83H heterozygous nonsense mutation c.1192C>T (p.Q398*) was detected in the patient. SEM revealed inconsistent dentinal tubules, and EDS showed that calcium and phosphorus were lower in the patient\'s dentin but higher in the enamel compared to the control tooth. Roughness measurements showed that AI patients\' teeth had rougher occlusal surfaces than those of the control tooth. Nanoindentation measurements showed that the enamel and dentin hardness values of the AI patients\' teeth were both significantly reduced compared to those of the control tooth. Compared to the wild-type FAM83H protein, the mutant FAM83H protein shows alterations in stability, hydrophobicity, secondary structure, and tertiary structure. These changes could underlie functional differences and AI phenotype variations caused by this mutation site.
CONCLUSIONS: This study expands the understanding of the effects of FAM83H mutations on tooth structure.
CONCLUSIONS: Our study enhances our understanding of the genetic basis of AI and may contribute to improved diagnostics and personalized treatment strategies for patients with FAM83H-related AI.
METHODS: Whole-exome sequencing (WES) and Sanger sequencing were used to confirm the mutation sites. Physical features of the patient\'s teeth were investigated using various methods including cone beam computer tomography (CBCT), scanning electron microscopy (SEM), contact profilometry (roughness measurement), and a nanomechanical tester (nanoindentation measurement). The protein features of wild-type and mutant FAM83H were predicted using bioinformatics methods.
RESULTS: One previously discovered FAM83H heterozygous nonsense mutation c.1192C>T (p.Q398*) was detected in the patient. SEM revealed inconsistent dentinal tubules, and EDS showed that calcium and phosphorus were lower in the patient\'s dentin but higher in the enamel compared to the control tooth. Roughness measurements showed that AI patients\' teeth had rougher occlusal surfaces than those of the control tooth. Nanoindentation measurements showed that the enamel and dentin hardness values of the AI patients\' teeth were both significantly reduced compared to those of the control tooth. Compared to the wild-type FAM83H protein, the mutant FAM83H protein shows alterations in stability, hydrophobicity, secondary structure, and tertiary structure. These changes could underlie functional differences and AI phenotype variations caused by this mutation site.
CONCLUSIONS: This study expands the understanding of the effects of FAM83H mutations on tooth structure.
CONCLUSIONS: Our study enhances our understanding of the genetic basis of AI and may contribute to improved diagnostics and personalized treatment strategies for patients with FAM83H-related AI.
摘要：
目的：目前对FAM83H基因不同位置的单核苷酸多态性（SNP）突变位点及其表型变化导致牙釉质发育不全症（AI）的研究不一致。我们确定了先前报道的杂合无义突变c.1192C>T（p。Q398*)中的FAM83H基因并对该突变诱导的牙体超微结构和化学成分变化进行了综合分析。此外,我们预测了受该突变位点影响的蛋白质特征。目的是进一步加深我们对FAM83H基因中不同突变位点引起的AI多样性的理解。
方法：使用全外显子组测序（WES）和Sanger测序来确认突变位点。患者牙齿的物理特征使用各种方法进行调查，包括锥形束计算机断层摄影（CBCT），扫描电子显微镜（SEM），接触轮廓术（粗糙度测量），和纳米机械测试仪（纳米压痕测量）。使用生物信息学方法预测野生型和突变型FAM83H的蛋白特征。
结果：一个先前发现的FAM83H杂合无义突变c.1192C>T（p。在患者中检测到Q398*）。扫描电镜显示牙本质小管不一致，EDS显示，与对照牙齿相比，患者牙本质中的钙和磷含量较低，但牙釉质中的钙和磷含量较高。粗糙度测量显示，AI患者的牙齿比对照牙齿的咬合面更粗糙。纳米压痕测量表明，与对照牙齿相比，AI患者牙齿的牙釉质和牙本质硬度值均显着降低。与野生型FAM83H蛋白相比，突变体FAM83H蛋白显示出稳定性的改变，疏水性,二级结构,和三级结构。这些变化可能是由该突变位点引起的功能差异和AI表型变异的基础。
结论：本研究扩展了对FAM83H突变对牙齿结构影响的理解。
结论：我们的研究增强了我们对AI遗传基础的理解，可能有助于改善FAM83H相关AI患者的诊断和个性化治疗策略。
方法：使用全外显子组测序（WES）和Sanger测序来确认突变位点。患者牙齿的物理特征使用各种方法进行调查，包括锥形束计算机断层摄影（CBCT），扫描电子显微镜（SEM），接触轮廓术（粗糙度测量），和纳米机械测试仪（纳米压痕测量）。使用生物信息学方法预测野生型和突变型FAM83H的蛋白特征。
结果：一个先前发现的FAM83H杂合无义突变c.1192C>T（p。在患者中检测到Q398*）。扫描电镜显示牙本质小管不一致，EDS显示，与对照牙齿相比，患者牙本质中的钙和磷含量较低，但牙釉质中的钙和磷含量较高。粗糙度测量显示，AI患者的牙齿比对照牙齿的咬合面更粗糙。纳米压痕测量表明，与对照牙齿相比，AI患者牙齿的牙釉质和牙本质硬度值均显着降低。与野生型FAM83H蛋白相比，突变体FAM83H蛋白显示出稳定性的改变，疏水性,二级结构,和三级结构。这些变化可能是由该突变位点引起的功能差异和AI表型变异的基础。
结论：本研究扩展了对FAM83H突变对牙齿结构影响的理解。
结论：我们的研究增强了我们对AI遗传基础的理解，可能有助于改善FAM83H相关AI患者的诊断和个性化治疗策略。
